In the proposed research, the chemistry of reactive electrophiles will be studied. This work involves both synthetic methodology development and mechanistic studies. In the development of new electrophilic synthetic methods, we will seek to apply the new chemistry to the preparation of biologically active compounds, including anti-depressant, anti-epileptic, analgesic, anti-psychotic, and anti-cancer drugs. The proposed research will lead to new methods for the preparation of commercial drugs, possibly leading to the more economical production of drugs. In the mechanistic studies, our work will provide insights to a variety of electrophilic reactions. Some of these mechanistic studies are directly related to biological systems, including NAD+ reduction, peptide cleavage reactions, acetylcholine chemistry, and electron transfer processes. PUBLIC HEALTH RELEVANCE: Project Narrative This project will examine chemical structures and chemical reactions related to a number of important biochemical processes. The studies will also strive to invent new methodologies for the preparation of pharmaceutical substances.